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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19-Jun-1997 to 04-Sep-1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Guinea Pig Maximisation test method. Furthermore, the LLNA test method is not considered to be suitable for fatty alcohols. Please refer to the attached document for further details.

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Japan SLC Co.
- Age at study initiation: 5 weeks
- Weight at study initiation: 304 to 355 g
- Housing: 5/cage; aluminium cages with stainless steel wire mesh floors (350 x 400 x 200 mm)
- Diet (e.g. ad libitum): standard pelleted guinea pig diet (RC-4), ad libitum
- Water (e.g. ad libitum): tap water 5 um-filtered, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +- 2
- Humidity (%): 50 +- 10
- Air changes (per hr): 17
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 24-Jun-1997 To: 04-Sep-1997

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
other: liquid paraffin
Concentration / amount:
3 and 6% intracutaneous induction, 50% epicutaneous induction; 3 and 10% epicutaneous challenge
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: liquid paraffin
Concentration / amount:
3 and 6% intracutaneous induction, 50% epicutaneous induction; 3 and 10% epicutaneous challenge
No. of animals per dose:
10 test, 5 control
Details on study design:
RANGE FINDING TESTS:
- 8 females
- concentrations for intracutaneous application: 10, 5, 3, 1, 0.3, 0.1, 0% in liquid paraffin
- concentrations for occluded epicutaneous application (presumably 7 days later): undiluted, 30 and 10% in liquid paraffin
- evaluated for skin irritation at 24, 48 and 72 hours after intracutaneous application
- evaluated for skin irritation at 3, 24 and 48 hours after epicutaneous application

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2, intracutaneous and occluded epicutaneous
- Exposure period: epicutaneous induction 7 days after intracutaneous induction; epicutaneous challenge 21 days after intracutaneous induction
- Test groups: 10 females
- Control group: 5 females
- Site: intracutaneous induction in the shaved skin area (~ 4 x 6 cm), symmetrically on both sides of the midline in the scapular region, test animals received (a), (b) and (c), controls received (a), (d) and (a); epicutaneous induction at initially exposed skin site shaved again, test animals received (e), control animals received (d)
- Frequency of applications: epicutaneous induction 7 days after intracutaneous induction
- Duration: epicutaneous induction 48 hours
- Concentrations: (a) 1:1 water-in-oil emulstion of Freunds complete adjuvant (FCA) and physiological saline, (b) test material at 3% in liquid paraffin, (c) 1:1 emulsion of test material at 6% in FCA and physiological saline, (d) liquid paraffin, (e) 0.2 ml of test substance at 50% in liquid paraffin

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21 days after intracutaneous induction
- Exposure period: 24 hours occlusive
- Test groups: 10 females
- Control group: 5 females
- Site: flank, clipped and shaved
- Concentrations: (f) 0.1 ml test substance at 10, 3 and 0% in liquid paraffin
- Evaluation (hr after challenge): 24 and 48 hours after removal of patches

OTHER:
- General condition
- Body weight
- Rechallenge: not required
Challenge controls:
Yes
Positive control substance(s):
yes
Remarks:
2,4-dinitrochlorobenzene and formalin, not concurrent, results from 12 tests at same testing facility

Results and discussion

Positive control results:
Evidence presented over a relevant time period that the strain of guinea pig did respond to known sensitisers

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
challenge: 0, 3 and 10%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
challenge: 0, 3 and 10%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
challenge: 0, 3 and 10%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no effects
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
challenge: 0, 3 and 10%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no effects
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

RESULTS OF RANGE FINDING TEST:

Following intradermal injection significant skin irritation was seen at concentrations of 5 and 10% persisting for 72 hours. The 3% concentration showed evidence of irritation at 24 hours only. Following topical application the undiluted material was irritant up to 48 hours, 2/4 guineapigs showed irritation at 10% while there was  no evidence of irritation with the 3% concentration.

RESULTS OF TEST
- Rechallenge: Not required.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In a reliable study, conducted to OECD guideline 406, Kalcol 2098 was not a skin sensitiser in guinea pigs. The study was performed in compliance with GLP.